Vasculopathy and vasculitis associated with levamisole-adulterated cocaine: a systematic review.

Immune checkpoint inhibitors (ICIs) have substantially improved the prognosis of many cancer patients but are also associated with various immune-related adverse events (irAEs). Kidney irAEs are relatively rare, with acute tubulointerstitial nephritis being the most common manifestation. However, some patients develop ICIs-associated glomerular diseases, including pauci-immune crescentic glomerulonephritis. In this report, we present the case of a 72-year-old man with lung squamous cell carcinoma treated with nivolumab, a monoclonal antibody targeting programmed cell death 1 (PD-1). The patient developed rapidly progressive glomerulonephritis a few weeks after initiating nivolumab therapy. Immunological tests yielded negative results, and a kidney biopsy revealed pauci-immune crescentic glomerulonephritis. Immunohistological examination confirmed programmed death ligand-1 (PD-L1) expression in the glomeruli. Despite intensive therapy, including corticosteroid pulse treatment, the patient's kidney function did not recover, necessitating maintenance hemodialysis. This is the first report demonstrating PD-L1 staining in injured glomeruli caused by anti-PD-1 therapy. Immunohistochemistry for PD-L1 may aid in diagnosing glomerulonephritis related to anti-PD-1 therapy.

Percutaneous renal mass biopsies with no viable lesional cells - Recognizing different histologic patterns can help predict nondiagnostic vs. true negative biopsy and guide clinical management.

Sclerosing mediastinitis (SM) is a rare condition characterised by extensive fibrous proliferation within the mediastinum. While some patients remain asymptomatic, others may present with chest pain, dyspnoea, haemoptysis, or complications such as superior vena cava syndrome or pulmonary hypertension. The aetiology of SM may be caused by infections, malignancies, autoimmune diseases, radiation therapy, or have idiopathic origins. We present a case of a 55-year-old man diagnosed with SM and granulomatosis with polyangiitis. The patient initially presented from an outside hospital with a large periaortic soft tissue mass, accompanied by symptoms of cough, shortness of breath, haemoptysis, and joint pain. Laboratory findings revealed elevated inflammatory markers and positive antineutrophil cytoplasmic antibody targeting proteinase-3. Imaging studies demonstrated abnormal mediastinal soft tissue encasing the thoracic aorta with subcarinal lymphadenopathy. Biopsy of the mass confirmed fibrotic tissue consistent with SM, and kidney biopsy revealed crescentic glomerulonephritis indicative of granulomatosis with polyangiitis. Treatment involved high-dose corticosteroids and rituximab, leading to significant improvement in overall patient status. The patient's follow-up revealed sustained remission, with resolution of lung infiltrates and decreased mediastinal mass size. Although the association between SM and antineutrophil cytoplasmic antibody-associated vasculitis remains unclear, our case highlights the importance of considering both diagnoses in a presentation of mediastinal fibrosis. Further research is warranted to clarify optimal management strategies for these rare conditions.

Background and Objectives: This study investigated and compared the efficacy of therapeutic plasma exchange (PEX) between antineutrophil cytoplasmic antibody (ANCA)-positive and ANCA-negative patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) presenting with diffuse alveolar haemorrhage (DAH) and rapidly progressive glomerulonephritis (RPGN). Materials and Methods: A total of 336 patients with ANCA-associated vasculitis were screened, and 34 patients with MPA/GPA receiving PEX for DAH or RPGN were included. PEX was performed a total of 5–6 times consecutively (three times a week × 2 weeks) in all 34 patients. All-cause mortality (ACM) and end-stage kidney disease (ESKD) were evaluated as poor outcomes of MPA/GPA. Clinical data and poor outcomes were compared between ANCA-positive and ANCA-negative MPA/GPA patients receiving PEX. Results: The median age of the 34 MPA/GPA patients was 67 years (15 men and 19 women), of whom two were diagnosed with ANCA-negative vasculitis. Among the 34 patients, 28 (82.4%) received PEX owing to RPGN, and 6 (17.6%) due to DAH. During follow-up, 13 patients (38.2%) died, and 15 (44.1%) progressed to ESKD. Serum protein and C-reactive protein levels at AAV diagnosis were higher in ANCA-positive MPA/GPA patients than in ANCA-negative patients, although the difference was not statistically significant. Similarly, there were no differences in ACM or ESKD between the two groups during follow-up. Survival analysis showed that ANCA-positive MPA/GPA patients did not have significantly different cumulative patient or ESKD-free survival rates compared to ANCA-negative patients. Conclusions: This pilot study is the first to demonstrate the clinical feasibility of PEX in managing severe and refractory ANCA-negative MPA and GPA.

Systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are distinct autoimmune disorders that rarely coexist. Their co-occurrence, known as SLE/AAV overlap syndrome, represents a clinically significant entity characterized by combined serological and histopathological features of both conditions. It is most commonly reported in females, with limited data on male patients. We describe a case of SLE/AAV overlap syndrome in a 38-year-old male with albinism who presented with progressive polyarthritis, generalized oedema, oliguria, and constitutional symptoms. Laboratory findings included elevated serum creatinine (170 µmol/L), nephrotic-range proteinuria (2.0 g/day), positive antinuclear antibodies (ANA: 4000 IU/mL), anti-dsDNA (800 IU/mL), P-ANCA (50.74 IU/mL), and low complement levels (C3 and C4). Urinalysis revealed RBC casts and dysmorphic red blood cells. Renal biopsy confirmed a dual diagnosis of lupus nephritis (class III + V) and crescentic glomerulonephritis with full-house immunofluorescence and ANCA positivity. The patient was treated with intravenous methylprednisolone pulses followed by low-dose cyclophosphamide (Euro-Lupus protocol). Upon clinical improvement, he was transitioned to oral mycophenolate mofetil, hydroxychloroquine, and enalapril. Within two months, he showed significant clinical and laboratory improvement with normalization of renal function (serum creatinine 73 µmol/L), reduction in proteinuria (to 298 mg/day), and a decrease in disease activity (SLEDAI-2K score of 2). This case emphasises the need for a high clinical suspicion in atypical autoimmune presentations. Early renal biopsy and prompt immunosuppressive therapy are crucial for favourable outcomes.

BackgroundAnti-glomerular basement membrane (GBM) disease represents the most severe form of crescentic glomerulonephritis. Previous studies demonstrated that Bowman’s capsule rupture contributed to the progression of crescentic glomerulonephritis. However, its role in anti-GBM disease remains unclear. The aim of this study was to investigate the prevalence and severity of Bowman’s capsule rupture in patients with anti-GBM disease and its clinical associations.MethodsA total of 72 patients diagnosed with biopsy-proven anti-GBM disease with complete clinical and pathologic data were retrospectively enrolled.ResultsExtensive Bowman’s capsule rupture occurred in 70 patients (97.2%) with a median percentage of 52.8% of all glomeruli on each kidney biopsy. The percentage of Bowman’s capsule rupture showed a strong association with kidney injuries (incidence of oligoanuria, eGFR, and serum creatinine on diagnosis; P < 0.001) and the levels of anti-GBM antibody (P = 0.013). Histologically, Bowman’s capsule rupture percentage was positively correlated with crescent percentage (P = 0.001) and increased proportion of cellular–fibrous crescents specifically (P = 0.047). The Kaplan–Meier analysis revealed significantly divergent outcomes in kidney survival (P = 0.006) and kidney recovery (P = 0.016) when the patients were divided into different groups according to the percentage of Bowman’s capsule rupture. The incorporation of Bowman’s capsule rupture into two proposed prediction models of risk stratification tool and renal risk score could improve their prognostic performance.ConclusionsBowman’s capsule rupture serves as both a distinct histopathological feature and a critical determinant of kidney injury in anti-GBM disease. More importantly, as a simple, standalone parameter, it demonstrates a robust predictive value for kidney outcomes in patients with anti-GBM disease.

Idiopathic inflammatory myopathies (IIM) are rare autoimmune disorders primarily affecting skeletal muscles, with occasional involvement of other organs and an increased risk of malignancy. Dermatomyositis (DM), a major IIM subtype, is characterized by proximal muscle weakness, distinctive skin manifestations, and characteristic biopsy findings. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), including microscopic polyangiitis (MPA), involve small- to medium-sized vessels and can affect the kidneys and lungs. Although uncommon, overlap syndromes between IIM and AAV have been described. We report two cases of DM-MPA overlap. The first involved a 67-year-old male with interstitial lung disease (ILD), muscle weakness, and proteinuria. The second concerned a 53-year-old female presenting with characteristic skin rash, arthralgias, proteinuria, and mild pulmonary involvement. Both patients received high-dose corticosteroids and cyclophosphamide (CYC), resulting in clinical and laboratory improvement, including resolution of proteinuria and improved pulmonary function, maintained over a 6-month follow-up. The literature review identified five relevant case reports and one case series. Fifteen patients from these six studies were included, predominantly female (13/15), with ages ranging from 15 to 84 years. DM was the most common IIM subtype (7/15), followed by polymyositis (PM) (6/15), inclusion body myositis (IBM) (1/15), and clinically amyopathic dermatomyositis (CADM) (1/15). MPA accounted for 87% (13/15) of AAV cases, while GPA was reported in 2/15. Renal involvement was frequent, often presented as pauci-immune crescentic glomerulonephritis, whereas pulmonary involvement was less common. MPO-ANCA was positive in 12/15 patients. Initial therapy typically involved corticosteroids, with or without immunosuppressants, tailored according to the dominant organ involvement. Outcomes were variable; most patients achieved remission, although some experienced persistent organ dysfunction. IIM-AAV overlap is rare but potentially severe, frequently involving renal, pulmonary, muscular, and occasionally cardiac systems. Early recognition and individualized immunosuppressive therapy can yield favorable outcomes. Multicenter studies are required to clarify the epidemiology, clinical spectrum, and optimal management of this complex syndrome, and further research is needed to elucidate underlying pathogenic mechanisms.

Patients with features of multiple systemic vasculitides are rare but do exist and can be diagnostically challenging. In particular, it can be difficult to distinguish granulomatosis with polyangiitis (GPA) with eosinophilia, proteinase 3 (PR3)-ANCA-positive eosinophilic granulomatosis with polyangiitis (EGPA), and overlap of GPA and EGPA in clinical practice. Nevertheless, in severe cases, rapid therapeutic decisions are required. We report such a life-threatening case of PR3-ANCA-positive vasculitis with eosinophilia, refractory to conventional therapy, that achieved remission with simultaneous biologic therapy using mepolizumab (MPZ) and rituximab (RTX) and provide a case-based review of the efficacy and safety of this dual biologic therapy. An 18-year-old man presented with cough, hemoptysis, leg purpura, and marked eosinophilia (4575/μL). Chest CT revealed alveolar hemorrhage (DAH). Proteinase 3 (PR3)-anti-neutrophil cytoplasmic antibody (ANCA) was positive, and skin biopsy showed leukocytoclastic vasculitis with eosinophil infiltration, consistent with EGPA. He was refractory to methylprednisolone (mPSL) pulse therapy and intravenous cyclophosphamide (IVCY), and DAH worsened, requiring non-invasive ventilation. Plasma exchange, MPZ (300mg), and RTX (375mg/m2 weekly × 4) were administered. DAH resolved rapidly after MPZ administration. Eosinophils dropped to 0/μL, but PR3-ANCA remained positive, and thereafter, nephritis developed. At 3months after disease onset, renal biopsy showed pauci-immune crescentic glomerulonephritis with little eosinophil infiltration. Additional mPSL pulses induced remission, which was maintained with MPZ and RTX. PR3-ANCA turned negative, and proteinuria resolved within 12months. Glucocorticoids (GCs) were discontinued after 2.5years, with a Vascular Damage Index (VDI) of 0. No serious infections or adverse events occurred. Although the development of glomerulonephritis after normalization of eosinophil count and DAH remission suggested possible EGPA-GPA overlap, the absence of granulomatous features and the potential phenotypic shift under anti-IL-5 therapy supported a final diagnosis of PR3-ANCA-positive EGPA. In life-threatening situations, the priority should be to initiate agents effective across both entities rather than to delay treatment until classification is certain. Our review suggests that simultaneous biologic therapy with MPZ and RTX can be effective with minimal adverse events and should be considered without hesitation in such critical cases.

The aetiology of crescentic glomerulonephritis is multifactorial, with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and anti-glomerular basement membrane (GBM) antibody disease being well-documented causes. Monoclonal immunoglobulin and immunoglobulin G4 (IgG4)-related diseases can also exacerbate kidney damage through varying mechanisms. However, cases where both ANCA and anti-GBM antibodies are positive, in the presence of serum M protein and elevated IgG4 levels, have not yet been reported. We herein report the first patient with dual ANCA and anti-GBM antibody-positive crescentic glomerulonephritis, along with monoclonal gammopathy and elevated IgG4 levels.

Significance of urinary and serum neutrophil gelatinase-associated Lipocalin in Antineutrophil cytoplasmic antibody-associated Vasculitis with glomerulonephritis.

ABSTRACT Paired box 8 (PAX8) and Wilms’ tumor 1 (WT1) of cap mesenchyme play important roles in tubular epithelial transition and podocyte maturation of the kidney. Parietal epithelial cells (PEC) progenitors demonstrate activity of these two factors in mature glomeruli. PECs can be activated into spindle cell crescents in crescentic glomerulonephritis (CreGN) or into podocyte hyperplasia in collapsing glomerulopathy (ColGN) based on histologic evidence. The study aimed to use PAX8 and WT1 stains to demonstrate the two transitional processes of mesonephros/metanephros and aberrant in CreGN, and ColGN. Immunohistochemical (IHC) stains for both PAX8 and WT1 were performed in fetal mesonephros/metanephros, adult negative controls, CreGN, and ColGN. Expressive patterns of PAX8 and WT1 in mesonephros/early fetal kidneys, adult kidneys, and aberrant glomerular changes were evaluated. PAX8 showed continuous nuclear expression in the parietal epithelium of mesonephros/metanephros, adult kidneys, & primordial podocytes, and consistent positivity in all renal tubules. WT1 showed strong nuclear and cytoplasmic expression within mature podocytes at all stages, despite some staining of WT1 in parietal epithelium. Cellular crescents and hyperplastic podocytes were strongly positive for PAX8, and only weakly positive in the nuclei of WT1. Our data support that PAX8+ PEC involve in mesenchymal-epithelial transition (MET) in renal tubules, a possible induction of early podocyte development, and aberrant epithelial proliferation of CreGN and ColGN. In addition, WT1 is fully devoted to podocyte maturation and is also partially involved in the aberrant epithelial proliferation of the two glomerular diseases.

Pauci-immune crescentic glomerulonephritis masquerading as goodpasture syndrome: ocular clues in a young adult: a case report.

Microscopic polyangiitis (MPA) is a rare ANCA-associated vasculitis that poses unique diagnostic and therapeutic challenges in seniors. We describe a 90-year-old female with diabetes, hypertension and heart failure who presented with anasarca and rapid renal failure. Evaluation revealed MPO-ANCA positivity, and renal biopsy confirmed pauci-immune crescentic glomerulonephritis. Her course was complicated by anemia and deep vein thrombosis. She was managed with high-dose corticosteroids, rituximab, and supportive hemodialysis, achieving improvement in renal function. This case highlights how comorbidities may obscure recognition of vasculitis and how assessment of frailty and baseline function are essential in weighing risks of immunosuppression in the seniors. Clinicians should maintain vigilance for ANCA-associated vasculitis in older adults with unexplained renal decline and tailor therapy to balance disease control with vulnerability to treatment toxicity.

Introduction: Novel molecular tools have the potential to improve current clinical and histology-based risk classification systems for various medical renal diseases including glomerulonephritis (GN). We aimed to assess the utility of gene expression for improving biopsy-based risk prediction in patients with GN with and without crescent formation. Methods: This retrospective case-control study used NanoString nCounter to measure the expression of 54 previously described inflammation, nephron injury, endothelium, and crescent-related genes in 335 archival, formalin-fixed paraffin-embedded native kidney biopsies, including a 288-biopsy discovery cohort representing a broad spectrum of crescentic GN subtypes, and an independent 47-biopsy validation cohort focused on ANCA-associated crescentic GN. Clinical, histologic, and gene expression data were compared. Results: Discovery cohort analysis demonstrated increased expression of 13 genes in crescentic GN cases that developed end-stage renal disease (ESRD) versus those that did not (false discovery rate <0.05). Within the 75-biopsy subset of ANCA-associated crescentic GN cases in the discovery cohort, this 13-gene set was found to be independently predictive of ESRD in multivariate Cox proportional hazards regression analysis (p = 0.015), with significant differentiation of high and low risk patients in the Kaplan-Meier renal survival analysis (log-rank test, p = 0.002). However, validation cohort analysis did not demonstrate significant improvement in risk stratification with the 13-gene set when compared with established clinicopathologic models. Conclusion: These results suggest that biopsy-based gene expression may provide the opportunity for improved risk stratification in crescentic GN; however, the genes evaluated in this study appear to have limited added clinical utility over existing risk scores.

Microfilarial infection is endemic in tropical regions, but renal involvement remains rare and under-recognized. The spectrum of biopsy-proven lesions is diverse, and its clinicopathological correlates are incompletely understood. We retrospectively analyzed renal biopsies that demonstrated intraglomerular microfilariae over a 6-year period. There were a total of seven patients (four males/three females; median age: 32 years, range 15-55). The presentations included nephrotic syndrome (2), acute nephritic syndrome (1), chyluria ± hematuria (2), and rapidly progressive renal failure (1). The biopsy spectrum showed non-proliferative glomerulonephritis (3), membranous pattern (1), amyloidosis (1), and crescentic lesions (2). Microfilariae were identified in glomerular (6) and peritubular (3) capillaries. DIF was positive in 3 (IgG and/or C3). All received diethylcarbamazine; 3 additionally received steroids. Clinical response was complete (4) and partial (3). Microfilaria-induced renal injury exhibits a wider morphological spectrum than previously recognized, including aggressive necrotizing crescentic glomerulonephritis. Awareness of this entity in endemic regions and timely institution of antifilarial therapy, with or without immunomodulation, can preserve renal function and improve outcome.

Rapidly progressive glomerulonephritis is a clinical syndrome that results in rapid decline in kidney function over a period of weeks to months. Its histological hallmark is extensive crescent formation. To determine the causes of crescentic glomerulonephritis (CGN) in the South African (SA) setting. The number of kidney biopsies performed at three tertiary hospitals during the 5-year study period was determined. Demographic data and serological test results were recorded. The underlying disease process of each of the CGN cases was defined under the three immunopathological categories: anti-glomerular basement membrane disease; immune complex-mediated; and pauci-immune vasculitis. There were a total of 980 native kidney biopsies performed at the three tertiary hospitals, namely, Chris Hani Baragwanath Academic Hospital, Charlotte Maxeke Johannesburg Academic Hospital and Helen Joseph Hospital, in Gauteng Province, SA, between 1 January 2015 and 31 December 2019. There were 43 crescentic glomerulo nephritidies (4.4%). The patients' ages ranged from 19 to 65 years, and 30 patients were female. The study comprised a majority of black patients (83.7%). Most CGN cases (39/43; 90.7%) were immune complex-mediated, and the remainder were anti-neutrophil cytoplasmic antibody mediated. The underlying cause of the 39 immune complex-mediated crescentic glomerulo nephritides was lupus nephritis in 32 (82%) cases, post-infectious glomerulonephritis (PIGN) in 2(5.1%), IgA nephropathy in 1 (2.6%) and 4 (10.2%) with an undetermined underlying cause. This study revealed the predominant cause of CGN to be lupus nephritis in 82.1% of patients, followed by PIGN in 5.1%. The prevalence of CGN was 4.4%. This study emphasises the variation in aetiologies of CGN in sub-Saharan Africa.

Systemic Granulomatous polyangiitis (GPA) can extend to rare organ involvement, including the heart which pose significant diagnostic and therapeutic challenges. A 26-year-old male with chronic sinusitis presented to clinic for evaluation of nasal crusting and bloody discharge (Image 1). He had a history of nasal polyposis resection. Laboratory evaluation was significant for leukocytosis and mild anemia. CXR showed nonspecific multifocal patchy infiltrates. Chest CT revealed numerous bilateral pulmonary nodules with central cavitation (Image 2). Immunological testing revealed the presence of c-ANCA and proteinase 3 (PR3) antibodies. GPA was suspected and the patient was started on prednisone. Bronchoscopy showed friable nasal mucosa with cobble stoning. Infectious workup was negative. He was initiated on high dose steroid with a plan to add rituximab (RTX). Few days later, he presented with chest pain, he was hypertensive and tachycardiac, he had elevated BNP and troponin. EKG showed no ST changes, but Echocardiogram revealed an EF of 50% with dilated left ventricle. Coronary vasculitis was suspected, cyclophosphamide (CYC) induction was initiated. Cardiac MRI demonstrated moderate systolic dysfunction with EF 34% and atypical myocarditis. Left heart catheterization (LHC) revealed disseminated vasculitis with diffuse involvement of distal coronary arteries. He was initiated on guideline-directed medical therpay and given RTX. A week later, he presented with elevated creatinine. Renal biopsy revealed ANCA-mediated focal crescentic glomerulonephritis. He underwent plasmapheresis with imporvement of his kidney function. A month later, he presented with recurrence of chest pain. Troponins were elevated, EKG demonstrated inferior ST elevation, and LHC revealed progression of coronary vasculitis. Repeat echocardiogram showed an EF of 15%. He was treated with steroids, and CYC. However, he continued to worsen, and eventually progressed to cardiogenic shock with multiorgan failure and was put on VA-ECMO support. The patient was transferred to a higher level of care center for LVAD and heart transplant. The nonspecific presentation of GPA often results in significant diagnostic delays, leading to increased morbidity and mortality. Cardiac complications are rare, posing severe risks. Standard treatment includes induction therapy with high-dose glucocorticoids combined with CYC or RTX for severe GPA. However, some cases remain refractory to therapy.

CC motif chemokine ligand 20 (CCL20), a chemokine involved in immune cell migration through its receptor CCR6, has been implicated in kidney inflammation in crescentic glomerulonephritis and acute kidney injury. However, clinical information for other kidney diseases is scarce. We have analysed CCL20 levels in plasma and urine from patients with diabetic kidney disease (DKD, n = 98) and autosomal dominant polycystic kidney disease (ADPKD, n = 85) treated according to the guidelines and studied their association with baseline characteristics and long-term (median follow-up 4.9 and 7.1 years, respectively) clinical outcomes. Single-cell kidney transcriptomics were mined to identify CCL20-expressing cells. Plasma CCL20 was higher in DKD and ADPKD than in a reference group: median 12.8 (3.5–33.2), 6.0 (1.2–19.2), and 0.0 (0.0–9.0) pg/mL, respectively. Urinary CCL20 was quantifiable in 48% of patients with DKD but not in the reference group. Transcriptomics data support a local kidney source of CCL20. In DKD, plasma CCL20 was higher in early compared to advanced CKD. Urinary CCL20 was higher in patients with A2 albuminuria than in those with other albuminuria categories. In ADPKD, higher plasma and urinary CCL20 levels tended to be associated with lower eGFR, higher albuminuria, and larger kidneys. However, no significant association was found between CCL20 levels and progression to kidney failure or death. In conclusion, CCL20 is increased in biological fluids and locally produced in CKD. While this may point to a potential role in risk stratification, further studies are necessary.

Antineutrophil Cytoplasmic Antibody (ANCA)-associated Vasculitis (AAV) is a life-threatening systemic autoimmune disease. Break of tolerance against either proteinase 3 or myeloperoxidase is key to the disease etiology. Innate and adaptive immune cells cooperate and contribute to the inflammatory necrotizing small-vessel vasculitis. AAV can affect every organ and frequently affects the kidneys. Necrotizing crescentic glomerulonephritis is associated with worse patient outcome. Anti-inflammatory and immunosuppressive treatments are effective in inducing acute vasculitis remission but are associated with treatment-related morbidity and mortality. In 2024, Kidney Disease: Improving Global Outcomes (KDIGO) provided an update of the Clinical Practice Guideline for the Management of AAV patients with kidney manifestation. A major aspect of the update is the consequent reduction of glucocorticoid exposure to diminish glucocorticoid toxicity. The C5a receptor blocker avacopan allows significant reduction of the cumulative glucocorticoids during AAV induction treatment, while increasing sustained remission and improving the glomerular filtration rate. Therefore, avacopan is now considered in the guideline as an alternative to glucocorticoids. Other topics covered by the KDIGO experts are the use of cyclophosphamide and rituximab or combinations thereof in patients with severe kidney involvement for inducing AAV remission. Moreover, considerations for the use of plasma exchange are provided.